LncRNA C9orf139 Promotes Acute Myeloid Leukemia Cell Proliferation by Sponging miR-24-3p to Upregulate TAOK1

Abstract

Objective

Long non-coding RNAs (lncRNAs) are critical in the pathogenesis of hematological malignancies, including acute myeloid leukemia (AML). However, the specific role and underlying mechanisms of the lncRNA chromosome 9 open reading frame 139 (C9orf139) in AML remain unclear. This study aimed to investigate the role and molecular mechanism of C9orf139 in AML development.

Methods

AML-related sequencing and microarray data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Significant lncRNAs and mRNAs influencing AML progression were identified and analyzed. A competing endogenous RNA network involving lncRNA–microRNA (miRNA)3–mRNA interactions was subsequently constructed. The expression levels of C9orf139, miR-24-3p, and human TAO kinase 1 (TAOK1) were assessed via real-time fluorescent quantitative polymerase chain reaction (PCR). Cell proliferation was evaluated via the Cell Counting Kit-8 (CCK8) assay, whereas Transwell assays were used to assess cell invasion and migration. Apoptosis was measured by Annexin V Fluorescein Isothiocyanate (FITC) double staining. Tumor formation in nude mice was assessed to examine the effect of C9orf139 on in vivo tumor growth. The C9orf139-miR-24-3p-TAOK1 regulatory axis was validated via dual luciferase reporter assays and RNA-binding protein immunoprecipitation (RIP). Western blot assays were used to assess the expression and phosphorylation of key proteins in the mitogen-activated protein kinase (MAPK) signaling pathway.

Results

Bioinformatics analysis identified C9orf139 and TAOK1 as differentially expressed genes that play key roles in AML pathogenesis. The C9orf139-miR-24-3p-TAOK1 axis was tightly linked to AML development, as confirmed by clinical sample analysis. In vitro, C9orf139 downregulation resulted in reduced proliferation, invasion, and migration and enhanced the apoptosis of AML cells. In vivo, the inhibition of C9orf139 significantly impaired tumor growth in nude mice. The regulatory axis was further validated. C9orf139 knockdown reduced the phosphorylation levels of the key MAPK pathway proteins, including Raf, mitogen-activated protein kinase kinase (MEK), and extracellular regulated protein kinase (ERK).

Conclusion

C9orf139 regulates AML progression by activating the MAPK signaling pathway through the C9orf139-miR-24-3p-TAOK1 axis.

Keywords

Acute myeloid leukemia / C9orf139 / MiR-24-3p / TAOK1 / Proliferation / Differentiation; CeRNA; MARK signaling pathway

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Funding

the Youth Talent Science and Technology Project of Health Commission of Changzhou(QN202223)

Education Research Project of Nanjing Medical University(2023ZC086)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to the Huazhong University of Science and Technology